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Personalized Health(care): more than ‘just’ targeted medicines
Professor of Personalized Healthcare Head Radboud Center for Proteomics, Glycomics and Metabolomics Coordinator Radboud Technology Centers
Senior Scientist Integrator Biomarkers
Prof Alain van Gool
Rotary Oss 3 March 2016
Scientific lead DTL-Technologies Head Biomarker Platform
My background in personalized health(care)
8 years academia (NL, UK)
(molecular mechanisms of disease)
13 years pharma (EU, USA, Asia)
(biomarkers, Omics)
4 years med school (NL)
(personalized healthcare, Omics, biomarkers)
4 years applied research institute (NL, EU)
(biomarkers, personalized health, nutrition)
1991-1996 (PhD)
1996-1998 (post-doc)
2009-2012 (visiting prof)
1999-2007 2007-2009 2009-2011
2011-now
2011-now (prof)
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A person / citizen / family man (adventures in EU, USA, Asia)
Alain van Gool, Rotary Oss, 3 Mar 2016
2016 (Scientific lead DTL-Technologies)
2016 (Head Biomarker Platform)
3 Alain van Gool, Rotary Oss, 3 Mar 2016
Consider individual differences in life science research
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Source: Chakma, Journal of Young Investigators, 16, 2009
Principle of Personalized Medicine
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• The right drug for right patient at right dose at right time • Molecular biomarkers as key drivers of patient selection • = Precision medicine or Targeted medicine
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Crash course in molecular biology
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DNA, protein, cell, tissue, system biology
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Biomarkers
{Biomarkers definition working group, 2001 }
Definition: ‘a characteristic that is objectively measured and evaluated as
an indicator of normal biological processes, pathogenic processes, or
pharmacologic responses to a therapeutic intervention’
Or ‘Whatever works in adding value’
Molecular biomarkers provide a molecular impression of a biological system
(cell, animal, human)
Biomarkers can be various sorts of data, or combinations thereof
Dutch CC meeting ‘Personalized Health Care”
Ede, 2 October 2013
Alain van Gool
Lecture LKCH, UMC Utrecht
29 October 2013
Alain van Gool
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Example: B-RAF mutations and melanoma
{Miller and Mihm,
2006}
8 Alain van Gool, Rotary Oss, 3 Mar 2016
Mechanism of pathophysiology in BRAF mutated tumors
• B-RAFV600E mutation: cell is always growing and becomes a cancer cell
• RAF inhibitors will block pathway, block cell growth and inhibit cancers that have a B-RAFV600E mutation
• Prevalence of B-RAFV600E is base for patient selection:
• Melanoma (60%), colon (15%), ovarian (30%), thyroid (30%) cancer
V600E
Kinase domain
{Roberts and Der, 2007}
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Clinical efficacy of Vemurafenib (PLX-4032, Zelboraf)
Key biomarkers: Stratification: BRAFV600E mutation Mechanism: P-ERK Cyclin-D1 Efficacy: Ki-67 18FDG-PET, CT Clinical endpoint: progression-free survival (%)
{Source: Flaherty et al, NEJM 2010} {Source: Chapman et al, NEJM 2011}
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Vemurafenib trials
108 clinical studies
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Emerging Personalized / Precision / Targeted Medicine
2010:
5% of drugs in pipeline had companion diagnostic biomarker test
2015:
80%
50%
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Optimal Personalized / Precision / Targeted Medicine
People are more than linear pathways
Moving to Personalized Health(care)
“The term "personalized medicine" is often described as providing "the
right patient with the right drug at the right dose at the right time."
More broadly, "personalized
medicine" may be thought of as the tailoring of medical treatment to the individual characteristics, needs, and
preferences of a patient during all stages of care, including prevention,
diagnosis, treatment, and follow-up.”
(FDA, October 2013)
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Societal need in efficient personalized health(care)
{Source: prof Jan Kremer}
Towards cost effective care, less cure
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Personal need in efficient personalized health(care)
It’s personal !
‘I want to stay healthy.’ ‘If not, how do I get healthy?’
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My route to Personalized Health(care)
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Analogy: TOMTOM
GPS to a location
Amsterdam
Traffic jam
Amsterdam
Route 1 Route 2
= Default Traffic jam near Utrecht Alternative route
20 Alain van Gool, Rotary Oss, 3 Mar 2016
Personalized Health(care) model
GPS to health
Health
Route 1 Route 2
= Default First signs of disease risk
Alternative route
Now
Disease risk
Health
Now
Health
21 Alain van Gool, Rotary Oss, 3 Mar 2016
3 key aspects of personalized health(care)
‘I want to stay healthy. If not, how do I get healthy?’
1. What to measure?
2. How much can it change?
3. What should be the follow-up for me?
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Exponential technological developments • Next generation sequencing
• DNA, RNA • Risk analysis and therapy selection
• Mass spectrometry • Proteins, metabolites • Monitoring of disease and treatment effects
• Imaging
• Non invasive images, real time
• Spatial view of intact organs and organisms
500
1000
1500
2000
m/z
5 10 15 20 25 30 35 40 Time [min]
23 Alain van Gool, Rotary Oss, 3 Mar 2016
News from a molecular biomarker lab • Mass spectrometry analysis of glycoproteins in human plasma • 1 microliter analysis: detection of 100K features in one scan • ~40.000 peptides of which >80% contain sugar modification • Diagnose patients and identify new biomarkers
500
1000
1500
2000
m/z
5 10 15 20 25 30 35 40 Time [min]
Proof of principle study:
{Translational Metabolic Laboratory, Radboudumc, unpublished data}
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New data (generators, owners)
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Demo room
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Personalized advice
Action
Selfmonitor Cloud
Lifestyle Nutrition Pharma
DIY monitoring of vital signs
28 Alain van Gool, Rotary Oss, 3 Mar 2016
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• Measure your brain waves (EEG)
• Recognize conditions for maximal concentration or relaxation.
• Use device to train.
DIY brainwave monitoring
29 Alain van Gool, Rotary Oss, 3 Mar 2016
DIY blood biomarker analysis
• Measure key biomarkers in one drop of blood at few $ per test panel
• Download data to your smartphone to monitor your own trend
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• DIY sequence your genome and/or your microbiome genome • at a provider, at a pharmacy, at home
• Take your genome to the doctor • Have a personalized healthcare advice
DIY sequencing
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23% chance blond hair
DIY sequencing
3.1% Neanderthaler DNA
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Genetic risk lung cancer → don’t smoke !
DIY sequencing
No expected adverse reaction to Warfarin
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‘insideables’
‘wearables’
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Try-outs at REshape Center of Health(care) Innovation
Lucien Engelen
… but not all data is useful data !
3 key aspects of personalized health(care)
‘I want to stay healthy. If not, how do I get healthy?’
1. What to measure?
2. How much can it change?
3. What should be the follow-up for me?
38 Alain van Gool, Rotary Oss, 3 Mar 2016
Translation is key in personalized health(care)
Personal profile data
Knowledge
Understanding
Decision
Action
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Translation is key in Personalized Healthcare !
“I’m afraid you’re
suffering from an
increased IL-1β and
an aberrant miR843
expression”
Adapted from:
?
40 Alain van Gool, Rotary Oss, 3 Mar 2016
Personalized health(care) model Personalized Intervention
of patients-like-me Personal thresholds of persons-like-me
Big Biomarker Data
Molecular Non-molecular Environment …
Ho
meo
sta
sis
A
llo
sta
sis
D
isease
Time
Disease
Health
Selfmonitoring
Adapted from Jan van der Greef, TNO
Personal profile
Personalized health
Personalized medicine
{See eg Chen … Snyder, Cell 2012, 148: 1293}
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Need for optimal quality in health biomarker analyses
Test, interpret, advice
“Post-traumatic Test Syndrome” ?
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Personalized health(care) monitoring as part of our lives
• Monitor on background
• Alert when you are at risk
• Advice what to do
Examples from car dashboard:
• Empty gas tank
• Traffic jam ahead
43 Alain van Gool, Rotary Oss, 3 Mar 2016
Acknowledgements
Ron Wevers
Jolein Gloerich
Hans Wessels
Dirk Lefeber
Monique Scherpenzeel
Leo Kluijtmans
Lucien Engelen
Nathalie Bovy
Paul Smits
Maroeska Rovers
Bas Bloem
the Technology Centers
and many others
www.radboudumc.nl/personalizedhealthcare
www.radboudresearchfacilities.nl
www.radboudumc.nl/research/technologycenters
alain.vangool@tno.nl
alain.vangool@radboudumc.nl
www.linkedIn.com
www.slideshare.net/alainvangool
Many collaborators and funders
Jan van der Greef
Ben van Ommen
Bas Kremer
Lars Verschuren
Ivana Bobeldijk
Marjan van Erk
Carina de Jongh
Peter van Dijken
Peter Wielinga
Robert Kleemann
Suzan Wopereis
and many others
CarTarDis
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